Lymphangioleiomyomatosis (LAM) is a rare disease that occurs primarily in women of reproductive age. Clinical manifestations include spontaneous pneumothorax, slowly progressive dyspnea, chylothorax, hemoptysis, and chylous ascites. The cardinal pathologic finding is a proliferation of immature-appearing, disorganized smooth muscle cells (LAM cells) in the lung and axial lymphatics. LAM cells react with monoclonal antibody HMB45 which recognizes melanocyte lineage-specific antigen(s). We report herein the comprehensive evaluation of 35 patients with LAM (age 42.3 +/- 8.6 yr). Most patients had exertional dyspnea (83%) and pneumothorax (69%). Most common abnormalities on pulmonary function tests were decreased DLco (83%), hypoxemia (57%), and airway obstruction (51%). By computed tomography, numerous thin-walled cysts throughout both lungs were found in all patients. Most patients (97%) had abnormal ventilation and/or perfusion lung scans. An unusual "speckling" pattern was observed on ventilation scans of 74% of patients. Common extrapulmonary features were renal angiomyolipoma (60%) and retroperitoneal adenopathy (77%). Bronchoalveolar lavage was performed in 16 patients and found to be safe. Percentage of LAM cells reactive with HMB45 was variable (17-67%) in lung biopsy specimens from 10 patients. Despite hormonal manipulation, the lung function of most patients continued to decline. More effective therapy will require a better understanding of the pathogenesis of LAM at the molecular and cellular level.